Enhancing Cancer Immunoprevention and Immunotherapy with Naturally Occurring Beta Glucans
Division of Cancer Prevention
Beta glucans (β-glucans) are polysaccharides – long chains of sugar molecules – found on the surface of microorganisms such as bacteria and yeast, as well as in some plants and edible fungi such as mushrooms. Natural foods containing β-glucans, including Shitake mushrooms, have been used for centuries for treating both infectious diseases and cancer in traditional Asian medicine, but with mixed success.
β-glucans are recognized as foreign by the human immune system, which targets them in a complex pathway involving the complement system, sending leukocytes (white blood cells) to destroy their microbial carriers. Until recently, researchers did not understand the complexity of the immune system reactions involved, explained Jun Yan, M.D., Ph.D., associate professor of medicine in the Tumor Immunobiology Program at the University of Louisville, Kentucky.
As research by Dr. Yan and others has now shown, the ability of β-glucans to increase the activity of leukocytes against cancer cells requires the presence of anti-tumor antibodies that activate the complement system. While the human immune system often does not recognize cancer cells in the bodies as invaders – and therefore does not produce antibodies to fight them – this discovery has important implications for the use of β-glucans as a non-toxic adjuvant for cancer-fighting monoclonal antibody treatments.
Monoclonal antibodies (mAbs) such as cetuximab, bevacizumab, and trastuzumab have improved the survival for many types of cancer. However, even the most effective mAb usually fails to eradicate all of the tumor cells in a patient. Although mAbs take advantage of part of the immune system, they often do not trigger a robust immune response in cancer patients.
By administering β-glucans along with mAbs, Dr. Yan hopes to increase the cancer cell killing effect over what would be achieved with a mAb alone by activating the complement system and triggering an innate immune response by leukocytes. Work performed by his laboratory using animal models of cancer has shown potential efficacy of this approach in several cancer types.*, **
With NCI funding***, Dr. Yan’s current research is investigating additional cellular and molecular mechanisms by which yeast-derived β-glucans exert their effect on the immune system. Better knowledge of these mechanisms of action will allow more effective incorporation into immunoprevention and immunotherapy regimens for cancer.
So far, his preliminary data has identified two cellular receptors that play critical roles in the early stages of an immune reaction to β-glucans. “In addition, we’ve found that β-glucans can also stimulate adaptive immune responses,” said Dr. Yan. The adaptive immune response, which ‘remembers’ previously encountered pathogens and other threats to the body, is what researchers are trying to harness to create anti-tumor vaccines. “And with any vaccine, you need an adjuvant treatment to augment efficacy,” he explained.
Dr. Yan and his colleagues are currently planning a clinical trial testing an oral formulation of particulate yeast β-glucans in combination with a dendritic-cell-based tumor vaccine for non-small-cell lung adenocarcinoma.
* Driscoll M, Hansen R, Ding C, Cramer DE, Yan J. Therapeutic potential of various beta-glucan sources in conjunction with anti-tumor monoclonal antibody in cancer therapy. Cancer Biology and Therapy, February 2009;8(3): 218-25.
** Salvador C, Li B, Hansen R, Cramer DE, Kong M, Yan J. Yeast-derived beta-glucan augments the therapeutic efficacy mediated by anti-vascular endothelial growth factor monoclonal antibody in human carcinoma xenograft models. Clinical Cancer Research, February 15, 2008;14(4):1239-47.
*** GRANT NUMBER: 1R01CA150947-01